Monocytes mediate osteoclastic bone resorption by prostaglandin production |
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Authors: | Jesus H Dominguez Gregory R Mundy |
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Institution: | (1) Department of Medicine, University of Connecticut School of Medicine, 06032 Farmington, Connecticut, USA;(2) Present address: Department of Medicine University of Arkansas for the Medical Sciences Little Rock, 72201 Arkansas |
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Abstract: | Summary Monocytes are frequently found adjacent to active bone resorption surfaces in both physiological and pathological situations
and may play a key role in bone resorption. There is strong circumstantial evidence that monocytes are precursors for osteoclasts
in vivo, and recently they have been shown to resorb devitalized bone directly. The present study shows that monocytes can
also resorb bone by stimulation of osteoclasts.
Live fetal rodent bones prelabeled with45Ca and cultured for 48–96 h in the presence of human monocytes or monocyte-conditioned medium released 80% more mineral than
bones cultured in control medium. Bone matrix sustained comparable resorption as demonstrated by a 2-fold decrement in the
extracted dry weights of the bones cultured in monocyte-conditioned medium. Histological examination of the bones cultured
with monocytes or monocyte-conditioned medium showed increased osteoclast number and activity when compared with bones cultured
in control medium. Known inhibitors of osteoclastic activity (phosphate 6 × 10−3M, cortisol 10−6M, and calcitonin 50 mU/ml) inhibited monocyte-conditioned medium-mediated bone resorption. The monocyte-conditioned medium
contained sufficient prostaglandin E to account for the bone resorption. Indomethacin 10−5M added to the monocyte cultures blocked monocyte-conditioned media-induced bone resorption and prostaglandin release.
These experiments suggest that monocytes stimulate osteoclastic bone resorption by prostaglandin production. Monocyte-induced
bone resorption is partly reversed by inhibitors of osteoclast function. Monocyte-induced osteoclastic bone resorption may
play an important role in physiologic bone remodeling and in bone destruction that occurs in chronic inflammatory diseases
such as rheumatoid arthritis and periodontal disease. |
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Keywords: | Monocytes Osteoclasts Bone resorption Prostaglandins |
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